tbuckley/cabot-search huggingface dataset:
Abstract 13824: Salsalate Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome
Authors: Alexander E Sullivan, Emily M Shardelow, Aaron W Aday, Quinn S Wells, Matthew S Freiberg, Joshua A Beckman
Journal: Circulation (2023)

Background: Insulin resistance accelerates systemic inflammation and vascular dysfunction. Salsalate suppresses inflammation and may improve insulin sensitivity and insulin-mediated, endothelium-dependent vasodilation. Hypothesis: We hypothesized that salsalate treatment would improve insulin-stimulated forearm blood flow (FBF) in volunteers with metabolic syndrome compared to placebo. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00760019) evaluating 4-weeks of salsalate 1.5 grams TID on insulin-stimulated FBF during an insulin clamp in patients with and without metabolic syndrome. Results: Nineteen patients received salsalate (13 metabolic syndrome and 6 healthy controls). Patients with metabolic syndrome were older (36.3 vs 57.1 years old, p=0.002) with higher BMIs (33.9 vs 25.5 kg/m 2 , p=0.001) and higher insulin levels (10.8 vs 4.3 μU/mL, p=0.01). Those with metabolic syndrome had impaired insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR, 2.66 vs 0.87, p=0.005) and Matsuda Index (MI, 5.81 vs 3.32, p=0.001). After salsalate treatment, insulin sensitivity was unchanged (Panel A &amp; B) and there was no significant reduction in insulin levels (Panel C) or inflammation by C-reactive protein (Panel D). Insulin stimulation increased FBF in patients treated with placebo (p=0.012) and salsalate (p=0.003), but salsalate blunted the FBF response in those with metabolic syndrome (p=0.022, Panel E). In multivariable linear regression, metabolic syndrome, HOMA IR, and MI associated with insulin-stimulated FBF independent of salsalate treatment. Conclusion: Salsalate improved neither insulin sensitivity nor systemic inflammation, and it blunted insulin-stimulated vasodilation in patients with metabolic syndrome. Salsalate does not modulate systemic inflammation and worsens arteriolar endothelial dysfunction in patients with metabolic syndrome.
Abstract 12523: A Case of Mesalamine Induced Myopericarditis
Authors: Ibrahim El-Mais, Sultani Nabil, Paul Nona
Journal: Circulation (2023)

Myopericarditis is a condition characterized by concurrent pericarditis and myocarditis, typically with evidence of myocardial involvement detected through elevated cardiac biomarkers or imaging studies indicating abnormal systolic function. Mesalamine is a well-established first-line IBD therapy. It can pose a rare yet serious risk of cardiotoxicity that may be difficult to distinguish from myocarditis presenting as an extra-intestinal manifestation of IBD. We report a case of myopericarditis in an 18-year-old male with newly diagnosed ulcerative colitis who was recently initiated on mesalamine. He presented with chest pain exacerbated by deep inspiration, shortness of breath, fever, palpitations, and elevated troponin levels. In addition to clinical presentation, an echocardiogram indicating left ventricular systolic dysfunction, and CMR revealing edema and late epicardial gadolinium uptake aided in the diagnosis. Prompt recognition and management of cardiovascular side effects associated with mesalamine use is crucial to prevent disease progression and development of complications. Clinicians should educate patients on the possible cardiovascular side effects of mesalamine and instruct them to seek medical attention if they experience any cardiac symptoms.
Abstract 16086: Impact of Amyloidosis on the Outcomes of Percutaneous Coronary Intervention Recipients: A Nationwide Analysis
Authors: Maharshi Raval, Sukhnoor Singh, Arthur Alencar, Yashvi Pethani, Sravani kommuru, Beegam Sulthana, Abhishek Chaudhary, Janani Prakash Babu, Iman Jasim Elttayef Elttayef, Sajid Siddiq
Journal: Circulation (2023)

Background: Interest in amyloidosis is increasing, primarily due to its high prevalence and recent advances in diagnostic and treatment modalities. The role of amyloidosis in aortic stenosis is established, and in coronary artery disease (CAD) outcomes are being reported. We aim to study the impact of amyloidosis on the outcomes of inpatient percutaneous coronary intervention (PCI) recipients. Methods: We conducted a cross-sectional cohort study using the nationwide inpatient sample (NIS) 2018-19. We included 457,730 adult inpatients with CAD managed with PCI and further divided by the presence of a co-diagnosis of amyloidosis. A logistic regression model was used to evaluate the odds ratio (OR) of the association between amyloidosis and various outcomes in PCI recipients.Results: Out of the total of 457,730 patients included, 30,905 (6.75%) had amyloidosis. Mean age (66.3 vs. 65.9), female sex (35.6% vs. 32.1%), and African American race (11.6% vs. 9.4%) were higher in the amyloidosis cohort (all P&lt;0.001). The amyloidosis cohort also had a higher incidence of acute kidney injury (AKI) (29.9% vs. 15.5%), complications of surgical care (1.7% vs. 0.7%), complications of cardiovascular implant (9.5% vs. 8.5%), major loss of function (54.7% vs. 27.8%), length of stay (LOS) in days (6.3 vs. 3.8), total charges in $ (166,001 vs. 121,718), and in-hospital mortality (4.7% vs. 2.6%) compared to non-amyloidosis cohort (all P&lt;0.001). Amyloidosis was associated with higher odds of in-hospital mortality (OR 1.3, 95CI 1.23-1.39, p&lt;0.001), AKI (OR 1.89, 95CI 1.83-1.94, p&lt;0.001), and complications of surgical care (OR 2.05, 95CI 1.87-2.26, p&lt;0.001) but not with complications of cardiovascular implant (OR 1.01, 95CI 0.97-1.05, p=0.703). Conclusions: Amyloidosis is associated with worse outcomes in inpatient recipients of PCI. Further studies are needed to assess the implications, safety, and outcomes of elective PCI in patients with amyloidosis.
Abstract 12559: Functional Autoantibodies Against Angiotensin II Receptor Type 1 and Endothelin-1 Receptor Type A Predict Adverse Remodeling and Cardiovascular Events After Acute Myocardial Infarction
Authors: Giovanni Civieri, Giulia Masiero, Martina Perazzolo Marra, Marta Vadori, Laura Iop, Emanuele Cozzi, Sabino Iliceto, Francesco Tona
Journal: Circulation (2023)

Introduction: Myocardial infarction is a leading cause of death worldwide. Although advances have been made in acute treatment, an incomplete understanding of left ventricular (LV) remodeling (LVR) processes has limited the effectiveness of therapies to reduce late-stage mortality. Hypothesis: We hypothesized that autoantibodies (AAs) activating angiotensin II receptor type 1 (AT1R-AAs) and endothelin-1 receptor type A (ETAR-AAs) are associated with LVR after ST-elevation myocardial infarction (STEMI) and with recurrent major adverse cardiac events (MACE). Methods: We studied 131 STEMI patients (age 61±11 years, 112 males) treated with primary percutaneous coronary intervention between February 2021 and January 2022 at Padua University Medical Center. Within 48 hours of admission standard 2D echocardiography was performed and blood samples were obtained for AAs level measurement. Echocardiography was performed at 6 months repeatedly in all patients. The endpoint was LVR, defined as an increase of 20% or more of LV end-diastolic volume index. Results: Overall, 41 (32%) patients experienced LVR. The titer for the autoantibodies was significantly higher in patients with LVR (p=0.009 for AT1R-AAs; p=0.01 for ETAR-AAs). The prevalence of AT1R-AAs and ETAR-AAs seropositivity was higher in patients with LVR (39% vs. 11%, p&lt;0.001 and 37% vs. 12%, p=0.001, respectively). At multivariable analysis, AT1R-AAs seropositivity was the strongest predictor of LVR (OR=4.25, p=0.002). Similarly, AT1R-AAs seropositivity was a strong predictor of recurrent MACE, both before (OR, 4.09; p = 0.006) and after (OR 19.6; p=0.002) adjusting for the confounding factors. Conclusions: Our results support the hypothesis that AT1R-AAs and ETAR-AAs concentration are a risk factor for LVR in STEMI patients. AT1R-AAs is also a predictor of recurrent MACE. These initial observations may set the stage for a better pathophysiological understanding of the mechanisms contributing to LVR.
Abstract 13822: Guideline Directed Medical Treatment in Patients With Heart Failure in China
Authors: Xiaotong Cui, Aiwen Yang, Long Lu, Jingmin Zhou, Hungta Chen, Feng Miao, Tianyu Zhao, Mengyu Xie, Xuwen Zhao, Phillip R Hunt, jiefu yang, Junbo Ge
Journal: Circulation (2023)

Introduction: Patients with Heart Failure (HF) are often treated at less than target dose or lack Guideline Directed Medical Treatments (GDMT), this has also been reported for patients with HF with reduced ejection fraction (HFrEF) in China. However, data on treatment patterns in different subgroups by disease onset and ejection fraction phenotypes is scarce. Research Question: What are the patient characteristics and treatment for HF in China in relation to concurrent guidelines? Aim: To describe characteristics of incident and prevalent patients with HF and treatment with GDMT (RAASi, BB and MRAs) for HFrEF patients in China prior to SGLT2i approval for HF. Methods: Data from the Heart Failure Registry at the Chinese Cardiovascular Association Heart Failure Center from Jan. 1, 2018 to July 31, 2021 was used. Data on the first 10 new HF inpatients each month is recorded on a case report form at discharge and 1-, 3- and 12-months follow-up. GDMT at discharge and 12 months was described for HFrEF patients. Results: We identified 32047 patients with HF: 21698 incident and 10349 prevalent cases, 13117 (40.9%) HFrEF, 6,368 (19.9%) HFmrEF, 10826 (33.8%) HFpEF and 1736 (5.4%) had no EF measurement. Mean age was 64.8 years in incident and 66.1 years in prevalent patients. A larger proportion of HFpEF patients were women than in other EF phenotypes. At discharge, 71.2% of incident and 75.7% of prevalent patients were treated with RAASi, 77.9% and 81.2% were treated with BB and 65.7% and 75.8% with MRA. Treatment was consistently lower at 12 months. In HFrEF 65.6% and 69.2% of incident and prevalent patients had three GDMTs at discharge; 37.3% and 39.9% at 12 months. Patient target/maximum tolerated dose for incident HFrEF patients was reached for17.6% (RAASi), 28.3% (BB) and 48.7% (MRA); for prevalent this was 24.8%, 38.4% and 50.8%. Conclusions: In this study on HF patients in Chinese clinical practice, 40% had HFrEF whereas the majority had preserved or mildly reduced EF. In the HFrEF patients, less than half of patients had three concurrent GDMTs at 12 months. Moreover, few patients received the target dose at 12 months and many discontinued treatment. These results show an urgent need for improved treatment strategies and effective implementation of new guidelines in China.
Abstract 16931: Network Analysis Identifies Partially Distinct Plasma Protein Associations Underlying HFpEF and HFrEF
Authors: Victoria Lamberson, Margherita De Marzio, Yimin Yang, Leo F Buckley, Pranav Dorbala, Brian Claggett, Peder L Myhre, Humaira Rasheed, Torbjorn Omland, Ron C Hoogeveen, Christie M Ballantyne, Josef Coresh, Bing Yu, Jacob Joseph, Yan Sun, Kimberly Glass, Amil M Shah
Journal: Circulation (2023)

Introduction: Underlying biological differences predisposing to heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction are unclear. We used a network analysis technique with plasma proteomics to uncover protein relationships differing between HFpEF and HFrEF. Methods: Among 4485 HF-free participants in the Atherosclerosis Risk in Communities study at Visit 5 (2011-2013), we used aptamer-based proteomics values (SomaScan v4; 4955 proteins) as inputs for the LIONESS network approach and reconstructed individual protein-protein interaction networks for each participant (4485 networks). Edge weights across these networks were regressed against incident HF to identify protein correlations statistically different between HFrEF vs no HF and HFpEF vs no HF. This resulted in two differential networks, one for HFpEF and one for HFrEF. Protein node pairs with an absolute difference in correlation of 0.45 were visualized. Two-sample Mendelian Randomization (MR) was used to identify potential causal associations between protein nodes and HFpEF or HFrEF using summary statistics from the Million Veterans Program. Results: Mean age was 75±5 years, 58% were women, and 193 HFpEF and 157 HFrEF events occurred at a median follow-up of 7 [IQR 6-8] years. The HFrEF network had 1205 protein nodes, 839 of which were in the largest connected component (LCC, Figure). In contrast, the HFpEF network had 592 proteins, 166 of which comprised the LCC. Only 257 proteins overlap between the two networks. MR identified 10 HFrEF node proteins with potential causal effects on HFrEF with 7 in the LCC, including 2 highly connected nodes (KIAA1549L, ZNF843) previously implicated in cardiac phenotypes. No causal associations were seen for HFpEF. Conclusions: Single-sample proteomics-based networks suggest different protein interactions characterize HFpEF and HFrEF. The HFrEF network was larger, more connected, and identified proteins with potential causal effects.
Abstract 12519: Biomarker Characterisation of Heart Failure Subtypes: A Population-Based Bioresource Linked Study
Authors: Chim C Lang, Mon M Oo, Chuang Gao, Christian Cole, Yoran Hummel, Magalie Guignard-Duff, Ify Mordi, Emily Jefferson, James Hare, Colin Palmer, Adriaan A Voors, Rudolf A de Boer, Jasper Tromp, Carolyn S Lam
Journal: Circulation (2023)

Background: Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study. Methods: We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany). Results: We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was &gt;0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days. Conclusions: In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.
Abstract 13831: Engineered Development: Directed Morphogenesis of an Embryonic Heart Tissue Model
Authors: Joshua R Gershlak, Harald Ott
Journal: Circulation (2023)

Introduction: The embryonic heart undergoes a complex looping morphogenesis, transforming a tube into the four-chambered organ. This phenomenon creates proper alignment leading to specification in the developing heart. Disruptions in the looping process are indicative for the onset of CHDs. Directed morphogenesis of an engineered tissue could be useful as a model of cardiogenesis. We created such a model system through the directed morphogenesis of an engineered tissue mimic of the embryonic heart. Methods: Embryonic heart tubes (EHT) were engineered to have an inner acellular layer surrounded by a thin iPS derived cardiomyocyte layer (A), mimicking the in vivo anatomy. In the embryo, cardiac looping is driven through both internal and external forces (B), leading to elongation of the tube resulting in a rightward rotation at the cranial end of the embryo and a dorsal deflection at the caudal end. We created a novel bioreactor (C) that mimics the external forces that are exhibited upon the heart within the embryo to direct morphogenesis. Our bioreactor allows for rotation on the cranial end, dorsal deflection on the caudal end, and tissue shortening on the entire tube. Results: EHTs were looped using the bioreactor system and found to recapitulate specific anatomical shapes (D). Looped EHTs were maintained for seven days via perfusion culture (E). After the culture period, ends of the looped EHTs were found to have fused together. Histological investigation discovered the generation of different complex anatomical structures (F). Namely, the generation of an intraventricular septum, cellular orientations that match measured angles within mammalian hearts, and ventricular shapes that closely resemble native heart. Conclusions: In conclusion, through directed morphogenesis, we created a model of the embryonic heart that matches native anatomical structures. This model could be further expanded to further study cardiogenesis or modified to study the onset of CHDs.
Abstract 15627: Accumulation of Chronic Conditions in Patients &lt;65 Years of Age Diagnosed With Atrial Fibrillation
Authors: Alanna M Chamberlain, Alvaro Alonso, Peter A Noseworthy, Bernard J Gersh, Sheila M Manemann, Susan Weston, Jill Killian, Euijung Ryu, Veronique L Roger, Konstantinos Siontis
Journal: Circulation (2023)

Background: Multimorbidity is common in atrial fibrillation (AF), particularly among older patients who generally have multiple cardiovascular and non-cardiovascular chronic conditions. However, less is known about the accumulation of chronic conditions in younger patients with AF. Methods: Patients aged &lt;65 with incident AF from 2013-2019 from a 27-county region in the Midwest (N=4907) were matched 1:1 on age (±5 years) and sex to referents from the same community. The index date for the matched pair was the date of first diagnosis of AF. Diagnosis of 20 other chronic conditions was ascertained from 3 years prior to index through 12/31/2022. Mean cumulative function curves were used to visualize the accumulation of conditions; Andersen-Gill models estimated associations between AF/referent status and accumulation of conditions. Results: The mean age was 55 years for both patients with AF and matched referents; 71% were male. In the 3 years leading up to AF diagnosis, only 4% of patients with AF had no additional chronic conditions and 69% had ≥3 chronic conditions. In contrast, 35% of referents had 0 and 32% had ≥3 chronic conditions. The accumulation of chronic conditions was accelerated in patients with AF compared to referents prior to AF diagnosis/index (Figure). After index, patients with AF had increased accumulation of chronic conditions (HR (95% CI): 1.93 (1.71-2.20), 1.82 (1.62-2.05), 1.68 (1.55-1.83), and 1.53 (1.44-1.64) for ages &lt;50, 50-54, 55-59, and 60-64 years, respectively). After 1 year, the differences were attenuated in all age groups with no difference observed between patients with AF and referents in the oldest age group (1.26 (1.08-1.46), 1.28 (1.11-1.47), 1.13 (1.02-1.24), and 1.05 (0.97-1.13) for ages &lt;50, 50-54, 55-59, and 60-64 years). Conclusion: Patients &lt;65 years with AF have an increased accumulation of chronic conditions compared to those without AF, in particular prior to their AF diagnosis and within the first year after AF diagnosis.
Abstract 13856: Echocardiographic Findings in Women With Ischemic Sudden Cardiac Death
Authors: Ida Hookana, Anette Eskuri, Lauri Holmstrom, Juha Vahatalo, Tuomas Kentta, Jani T Tikkanen, Lasse Pakanen, Juha Perkiomaki, Heikki Huikuri, Juhani Junttila
Journal: Circulation (2023)

Background: Majority of sudden cardiac deaths (SCD) are caused by coronary artery disease (CAD). Many women who experience SCD do not exhibit the traditional risk factors associated with SCD, which poses challenges in terms of SCD prevention and prediction. The data of SCD in women are limited as women are often underrepresented in SCD studies. Aim: The objective of this study was to investigate sex-specific echocardiographic findings in subjects with ischemic SCD. Methods: The study group consisted of 4392 subjects with ischemic SCD (20.2 % women) derived from the FinGesture study. The cause of death was determined at medicolegal autopsy. Pre-SCD echocardiography (ECHO) reports were collected from medical records. Ventricular and atrial dimensions as well as left ventricular mass (LVM) were categorized by using widely accepted thresholds. LVM was calculated using the LVM formula (LV Mass = (0.8 * [1.04 * ((LVEDD + IVSd + PWd) 3 - LVEDD 3 )]) + 0.6)). Left ventricular ejection fraction (LVEF) was classified into four categories: normal (&gt;55 %), mildly reduced (45-55 %), moderately reduced (35-45 %) and severely reduced (&lt;35 %). ECHO reports were available for 325 SCD victims (20.3 % women). Results: Left ventricular hypertrophy (LVH) was prevalent in 84.6 % of women and 76.4 % of men (p = 0.440). A thickened interventricular septum was observed in the majority of subjects in both sexes (84.8 % in women vs. 85.9 % in men, p = 1.000). Similarly, an enlarged left atrium was commonly found in both women (70.2 %) and men (72.3 %) (p = 0.856). The prevalence of dilated left ventricular end-diastolic diameter was 27.3 % in women and 30.1 % in men (p = 0.651). Overall, no significant differences were observed between the sexes in sex-adjusted ventricular or atrial dimensions. However, women with ischemic SCD were more likely to have a normal LVEF compared to men (63.4 % in women vs. 45.5 % in men, p &lt;0.001). Additionally, the prevalence of severely reduced LVEF was significantly lower in women than in men (5.4 % in women vs. 15.9 % in men, p = 0.005). Conclusions: LVH is a common finding in subjects with ischemic SCD. Women with ischemic SCD are less likely than men to have severely reduced LVEF prior to SCD. Additionally, in women, ischemic SCD tends to occur more often without a decrease in LVEF.